PL195582B1 - An iron-dextran compound for use as a component in a therapeutical composition for prophylaxis or treatment of iron-deficiency, a process for producing said iron-dextran compound and use of said compound for the preparation of a parenterally administrable therapeutical composition - Google Patents

Abstract

An iron-dextran compound for parenteral treatment of iron-deficiency anemia comprises hydrogenated dextran having a weight average molecular weight (Mw) between 700 and 1,400 Daltons, preferably approximately 1,000 Daltons, a number average molecular weight (Mn) of 400 to 1,400 Daltons and wherein 90 % by weight of the dextran has molecular weights less than 2,700 Daltons and the Mw of the 10 % by weight fraction of the dextran having the highest molecular weights is below 3,200 Daltons, said hydrogenated dextran having been subjected to purification by membrane processes having a cut-off value between 340 and 800 Daltons, in stable association with ferric oxyhydroxide. The compound is produced by using membrane processes to eliminate dextrans of higher molecular weights than approximately 2,700 Daltons and membrane processes to remove saccharides of molecular weights below approximately 340 Daltons from hydrogenated dextran before precipitating ferric hydroxide in the presence of said dextran followed by heat treatment and purification.

Description

The present invention relates to an iron (III) oxyhydroxide hydrogenated dextran association complex, a method for the preparation of the complex, the use of the complex, and a method for the preparation of an injection fluid containing the complex.

Worldwide, iron deficiency anemia is recognized as one of the most common - and perhaps the most common - pathological condition in humans. Iron deficiency anemia can also be a problem in modern pig and other domestic animals, in the absence of appropriate preventive measures.

Although iron deficiency anemia can often be prevented or treated with orally administered iron preparations, in many cases it is preferable to use parenteral iron preparations to avoid fluctuations in the bioavailability of the orally administered preparations and to ensure effective administration.

Thus, iron-containing preparations for parenteral use, i.e. for subcutaneous, intramuscular or intravenous administration, have been available to doctors and veterinarians for many years.

While various iron-containing substances have been used or suggested as ingredients in parenteral injection preparations for iron deficiency anemia, the most common preparations currently accepted are those containing the composite product iron (II) oxyhydroxide (or iron (III) hydroxide) associated with dextran. . Dextran is a polymeric carbohydrate produced by the Leuconostoc mesenteroides microorganism.

The iron-containing formulation for parenteral injection should of course meet a number of requirements, including the availability of iron for hemoglobin synthesis, no local or systemic side effects, and sufficient stability when stored at ambient temperature.

Iron-dextran formulations for the treatment of anemia have been in the market for decades, and many changes have been proposed to the formulation and choice of starting materials to increase the stability of such formulations and reduce the incidence of side effects associated with their administration.

Solutions to these problems are provided in the example patents discussed below.

US 2,885,393 (1959) describes a basic method for the preparation of an iron-dextran complex wherein the average molecular weight of the dextran is 30,000-80,000 daltons or less. The suitability of these complexes for the treatment of humans was not mentioned in that patent.

In US Re. 24642 (1959) gives a detailed explanation of the requirements for an iron solution intended for intramuscular injection. This patent relates essentially to a non-ionic iron (III) hydroxide dextran complex with an intrinsic intrinsic viscosity of about 0.025-0.25 at 25 ° C, and to a method for preparing such a complex by contacting the described dextran with iron (III) hydroxide prepared in situ in reaction of an iron (III) salt with a base, an alkali metal compound. No information is given on the desired molecular weight of the dextran, nor on the chemical modification of the dextran, other than partial depolymerization.

US 3,093,545 (1963) discloses certain details such as temperature and pH in an improved process for producing a product very similar to that produced by the process of the above-mentioned US Re. 24642.

GB 1200902 (1970) discloses that instead of producing iron (III) hydroxide in situ, it is preferable to pre-prepare iron (III) hydroxide under controlled conditions as such iron (III) hydroxide readily complexes with dextrans. It has been found that not only partially depolymerized dextran with an average molecular weight of e.g. 500-50,000 daltons, preferably 1,000-10,000 daltons, but also modified forms or derivatives of dextran such as hydrogenated dextrans, oxidized dextrans or treated dextranes may be contemplated as a theoretical possibility. alkaline treatment. However, only oxidized dextrans with an average molecular weight of 3,000 and 5,000 Daltons are specifically discussed in detail. Iron (III) hydroxide is prepared prior to contact with the dextran. This means that the resulting product is iron (III) oxyhydroxide on which the dextran forms a coating, in contrast to the more homogeneous products obtained by precipitation of iron (III) hydroxide in situ, i.e. in the presence of dextran.

DK 117730 (1970) relates to a process in which a molecular weight hydrogenated dextran

2,000 - 10,000 Daltons are reacted with iron (III) hydroxide in an aqueous medium. No

The average molecular weight of the dextran used in the examples is given. However, the reported intrinsic viscosity value is about 0.05, which would correspond to an average molecular weight of about 5,000 Daltons.

DK 122398 (1972) also discloses the use of hydrogenated dextran for the preparation of iron (III) hydroxide complex compounds and states that the product obtained with non-hydrogenated dextran is much less toxic. The subject of this patent specification is a process in which wet iron (III) hydroxide is mixed with dry hydrogenated dextran and, after the optional addition of citric acid or citrate, the mixture is heated and subjected to purification.

US 3,697,502 (1972) discloses a method for the preparation of an iron-dextran preparation in which citric acid is added to the dextran and an alkali metal hydroxide solution and iron (III) chloride solution are simultaneously added. The average molecular weight of the dextran used was 3,000 - 20,000 daltons. In the examples, dextran with a molecular weight of 7,000 and 10,000 daltons was used, respectively.

DK 129353 (1974) relates to an analogous method of producing an iron (III) hydroxide -dextran derivative, the average molecular weight of the dextran being 50,000 daltons or less, and the end groups of the polymer chains have been modified by converting the terminal reducing anhydroglucose groups to the corresponding carboxyl groups. While the range for the molecular weight of the dextran is reported to be very broad, being 500-5,000 Daltons, preferably 1,000-10,000 Daltons, the only dextran given as an example had an average molecular weight of 5,000 Daltons.

DK 129942 (1974) is similar to the above mentioned DK 129353 and relates to the preparation of complexes of iron (III) hydroxide with dextranohepton acid or dextrinheptonic acid. Heptonic acids are prepared by hydrolysis of the corresponding cyanohydrins.

US 4,827,945 (1989) and US 5: 102652 (1992) relate to superparamagnetic metal oxides, such as iron oxides, coated with or bound to polymeric substances such as dextran. This polymer is contacted with a mixture of metal oxides in two different oxidation states to form a complex superparamagnetic product which is then oxidized to convert all metal oxides to the highest oxidation state. This product is particularly useful as a contrast agent in medical diagnostic nuclear magnetic resonance imaging. However, it is also mentioned that it can be used to treat iron deficiency anemia. The molecular weight of these polymers, including carbohydrates such as dextran, is preferably 5,000-250,000 daltons.

GB 1,076,219 describes a method for the preparation of an iron preparation in which iron (III) hydroxide is bound to a complexing agent consisting of sorbitol, gluconic acid and an oligosaccharide in appropriate proportions, the main component being sorbitol. In one example, a hydrogenated dextran with an average molecular weight of about 1000 Daltons was used as the oligosaccharide. It can be concluded from the described process for producing dextran that the content of very low molecular weight components must be high. However, it is essential that a large amount of the hydrogenated dextran monomer, i.e. sorbitol, is present during the complex formation. It was found that sorbitol and polyglucose oligosaccharide have a positive effect on the formation of homogeneous complexes, which reduces the toxicity and increases the absorption of iron preparations.

RU 2093577 describes a method for producing dextran by acid hydrolysis followed by chromatographic purification. Dextran with an average molecular weight of about 1000 Daltons was obtained.

Despite the numerous attempts to improve the iron-dextran formulations for treating anemia disclosed in the above patents, the prior art formulations still suffer from some drawbacks.

In some patients, these preparations may cause delayed hypersensitivity or severe anaphylactic side effects, such as dyspnoea, hypotension, shock and death. Other toxic reactions can also occur.

Moreover, some of the preparations used so far do not meet the current stability requirements. Instability can be manifested by gelation of the liquid or precipitation of iron hydroxide or oxyhydroxide.

Based on research, tests and practical experience, it has now been found that the disadvantages discussed above are related to the presence, albeit in small amounts, of insufficiently hydrolyzed

Relatively high molecular weight dextran used as starting material as well as with the presence of low molecular weight saccharides therein.

It is generally believed that a higher risk of anaphylactic reactions is associated with high molecular weight dextrans rather than with low molecular weight dextrans. Indeed, the current practice to reduce the risk of anaphylactic reactions during clinical administration of dextrans is to pretreat the patient by injection of a low molecular weight dextran, such as a weight average molecular weight Mw dextran of about 1000 Daltons.

The preparation of the dextran typically involves the acidic hydrolysis of the higher molecular weight dextran, followed by isolation and purification, including precipitation of the dextran, e.g. from an aqueous solution by the addition of e.g. alcohol.

In such precipitation, not only the desired dextran fractions but also any higher molecular weight dextran precipitate, therefore the recovered dextran fraction often contains high molecular weight dextrans which have not been cleaved by the preceding acid hydrolysis.

Since even a very low concentration of high molecular weight dextrans can cause unpredictable and often severe anaphylactic reactions, it is necessary for the present invention to avoid the presence of such dextrans by replacing or supplementing known precipitation methods with membrane processes that allow very efficient removal of high molecular weight dextrans prior to contact. the desired dextran fraction with iron compounds.

However, it has been found that removal of the higher molecular weight dextran from the desired weight average molecular weight dextran fractions of e.g. 1000 Daltons does not ensure that the resulting iron-dextran complex will be non-toxic and stable. It has also been found that difficulties are posed by the presence of low molecular weight carbohydrates such as monosaccharides produced by the hydrolysis reaction.

Hitherto the presence of such saccharides has been considered to be of minor importance. However, when dextran containing such saccharides is reacted with iron, precipitation of iron (III) hydroxide in its solution not only produces iron-dextran association compounds, but also these saccharides combine with iron to form complex or associative compounds.

However, these saccharide-based iron compounds are much less stable than dextranironase compounds, and in aqueous solutions they increase the concentration of free iron (III) ions and low molecular weight saccharides such as glucose.

As is known, the free iron (III) ions present in parenteral preparations have a toxic effect. Moreover, it has been found that not only iron (III) ions, but also low molecular weight saccharides cause instability of aqueous iron-dextran solutions due to precipitation and / or gel formation, which can lead to complete solidification of the solution within a few days or months. In addition, the presence of low molecular weight saccharides appears to increase the parenteral toxicity of the iron-dextran solution, apparently because these saccharides interfere with the binding of the iron compounds to the dextran, forming free or only weakly bound iron (III) ions.

Although the linkage between low molecular weight saccharides and iron compounds is rather weak, it sufficiently interferes with efficient removal of saccharides and free iron compounds in the dialysis process, which is usually applied to iron-dextran solutions in the final processing step.

Thus, for the present invention, it is essential that the dextran fraction must be purified using membrane processes to remove low molecular weight saccharides, before using this fraction in a reaction that produces iron-containing complexes or associations.

The invention relates to an association complex of iron (III) oxyhydroxide and hydrogenated dextran with a weight average molecular weight (Mw) of 700-1400 daltons, preferably about 1000 daltons, the number average molecular weight (Mn) of 400-1400 daltons, whereby 90% by weight of the dextran is by weight and the Mw of the 10 wt% dextran fraction with the highest molecular weight is less than 3200 daltons, and this hydrogenated dextran has been purified using membrane processes at a cutoff of 340-800 daltons, for use as a therapeutic agent component for prophylaxis or treatment iron deficiency in animals or humans by parenteral administration.

PL 195 582 B1

Preferably, the association complex is the only or one component of the dry powder.

Preferably, this powder has an iron content of 15-45% by weight.

Preferably, the associative complex is dissolved or dispersed in the aqueous liquid, and in particular it is dissolved or dispersed in the aqueous liquid in such an amount that the iron content of the resulting solution or dispersion is 5-20% w / v.

The invention also relates to a method for producing an association complex of iron (III) oxyhydroxide and hydrogenated dextran as defined above, according to which the association complex is prepared by reducing the molecular weight by hydrolysis and converting aldehyde end groups in dextran to alcohol groups by hydrogenating the dextran; combining the hydrogenated dextran as an aqueous solution with at least one water-soluble iron (III) salt; a base is added to the resulting solution to form iron (III) hydroxide and the resulting mixture is heated by converting the iron (III) hydroxide to iron (III) oxyhydroxide in the form of an associative compound with dextran, the method being characterized by hydrolyzing but prior to combining with a water-soluble iron (III) salt, the dextran is purified using one or more membrane processes with a cut-off suitable for retaining dextran with a molecular weight greater than 2700 daltons, followed by optional further hydrolysis followed by one or more membrane processes with a cut-off of 340-800 daltons.

Preferably in the next steps of this method:

an aqueous solution is prepared containing the obtained hydrogenated dextran and at least one water-soluble iron (III) salt;

the pH of this aqueous solution is adjusted to above 10 by addition of a base;

this mixture is heated to above 100 ° C until a black or dark brown colloidal solution is obtained, filterable through a 0.45 µm filter; and purifying and stabilizing the solution by filtration, heating and membrane processes and adding one or more stabilizers and optionally drying the solution to obtain the desired iron-dextran compound as a stable powder.

Preferably the hydrogenation of the dextranes is carried out with sodium borohydride in an aqueous solution.

Preferably, the solution is stabilized by the addition of at least one salt of an organic hydroxy acid, preferably selected from among citrate.

The invention further relates to the use of an association complex of iron (III) oxyhydroxide and hydrogenated dextran having a weight average molecular weight (Mw) of 700-1400 daltons, preferably about 1000 daltons, a number average molecular weight (Mn) of 400-1400 daltons, with 90% by weight of the dextran has a molecular weight of less than 2,700 daltons and the Mw of the 10 wt% dextran fraction with the highest molecular weight is less than 3,200 daltons, and this hydrogenated dextran has been purified using membrane processes at a cutoff of 340-800 daltons to produce a prophylactic parenteral medicament or treating iron deficiency anemia in animals or humans.

The invention also relates to a method for the preparation of an injection fluid containing the compound ferriodextran, characterized in that the associative complex defined above in the form of a dry powder is dissolved in an aqueous medium, if necessary the pH is adjusted, optionally a stabilizer is added and the fluid is sterilized by filtration before filling. ampoules or vials or by autoclaving after filling into ampoules or vials.

The invention also relates to a process for the preparation of an injection fluid containing an iron-dextran compound, characterized in that the fluid obtained as defined above is purified, the iron content and the pH value are adjusted, stabilized and sterilized by filtration before filling into ampoules or vials or by autoclaving after filling into ampoules or vials.

Thus, injection fluids can be prepared by dissolving a powder containing an iron-dextran compound, adjusting the pH value, sterilizing by filtration, and filling into sterilizable ampoules or vials.

Alternatively, the drying operation is omitted and the injection fluid is prepared from the purified solution without intermediate drying it.

PL 195 582 B1

The terms "weight average molecular weight" and "number average molecular weight" mean the respective average molecular weight at the time of complex formation, calculated for all dextran molecules of increasing molecular weight, beginning with the monomer.

It is believed that the reason why dextrans with the above-defined molecular weight distribution have not found industrial application in the preparation of ferro-dextran compounds is due to the lack of sufficient attention to the presence of low molecular weight saccharides as causes of toxicity and inferior stability, and not paying sufficient attention to the fact that that dextrans with a weight average molecular weight of about 1000 Daltons are better tolerated by humans and animals than the higher molecular weight dextrans traditionally used in iron preparations.

When used for parenteral administration, the said compound is dissolved or dispersed in an aqueous liquid and can be sold as such, preferably the iron content is 5-20% w / v. Moreover, the compound is sufficiently stable to be dried without decomposition in a known drying process such as spray drying, so that the compound can also be sold as the sole ingredient or one of the ingredients of a dry powder. The iron content of such a powder is usually 15-45% by weight.

In relatively low molecular weight dextrans, such as those used in the invention, the effect of end groups (partially hydrogenated aldehydes) on the polymer chains is significantly more pronounced than in higher molecular weight dextrans, as the number of functional end groups is greater relative to weight. . These end functional groups deteriorate stability due to the reaction of Fe ³⁺ with low molecular weight saccharides. Thus, the absence of Fe ³⁺ and low molecular weight saccharides is even more important than when using higher molecular weight dextrans.

The following examples illustrate the invention.

Example 1 (i) Hydrolysis and hydrogenation of dextran

2.522 kg of hydrolyzed dextran, collected as filtrate from a membrane that cuts the <5000 Daltons fraction, was hydrolyzed at pH 1.5 at 95 ° C.

The hydrolysis was controlled by gel permeation chromatography (GPC) chromatography and stopped by cooling the reaction mixture when the molecular weight of the hydrolyzed substance was found to reach the desired value, i.e. a weight average molecular weight of 700-1400 Daltons.

Hydrolysis yielded low molecular weight dextran, but glucose was also produced. After cooling and neutralization, glucose and ultra-low molecular weight oligomers were reduced using membrane processes with a cutoff of 340-800 Daltons. Upon completion of this process, the dextran content was determined by optical rotation (a _D ~ 200) to be 1.976 kg, and the reducing sugar content determined using Somogyi's reagent was 36.8%.

The reducing capacity was reduced by treatment with sodium borohydride. To 1.976 kg of dextran was added 57 kg of sodium borohydride at basic pH.

After treatment with sodium borohydride, the reducing power was 1.5%.

The solution was then neutralized to pH <7.0 and subjected to deionization. Average molecular weight and molecular weight distribution were determined by chromatography.

The chromatography also shows that the above conditions are met, i.e. 90% by weight. % of dextran has a molecular weight below 2,700 Daltons and a weight average molecular weight (Mw) of 10 wt.%. the dextran fraction with the highest molecular weight is less than 3,200 daltons.

Mw was found to be 1,217 and Mn to 845 daltons. The final amount of dextran after deionization is 1320 kg based on optical rotation.

(ii) Synthesis of the iron-dextran complex

120 kg of dextran prepared as above in the form of an 18% solution was mixed with 150 kg of FeCk6H _; ABOUT.

93 kg of Na2CO3 as a saturated aqueous solution were added to this mixture with stirring, and then the pH of the mixture was adjusted to 10.5 with 24 liters of concentrated aqueous NaOH solution (27% w / v).

The mixture thus obtained was heated above 100 ° C until a black or dark brown colloidal solution was obtained, which was filtered through a 0.45 µm filter and then cooled. After

After cooling, the solution was neutralized with 12 liters of concentrated hydrochloric acid to bring the pH to 5.80 and purified by membrane processes to bring the chloride content of the solution below 0.68%, based on a 5% w / v solution. iron.

When the chloride content of the solution is less than that desired for an isotonic solution, sodium chloride is added, then the pH is adjusted to 5.6 and the solution is filtered through a 0.45 µm (or alternatively 0.2 µm) membrane filter.

The solution is spray dried and the iron-dextran complex in powder form is ready for sale or further processing.

Alternatively, no spray drying is performed, but the solution is used for the direct preparation of injection fluids with an iron content of e.g. 5% as described above.

When an iron-dextran complex is used in powder form for the preparation of injection or infusion fluids, the powder is dissolved in an aqueous medium, the pH is checked and adjusted if necessary, and then the solution is filled into ampoules or vials after sterilization by filtration. Alternatively, sterilization may be performed by autoclaving after filling into ampoules and vials.

Example 2 (i) Hydrolysis and hydrogenation of dextran

This synthesis step was carried out as described above under (i) in Example 1, except that 54 kg of sodium borohydride was used, thus the reduction capacity was reduced to 3.0%.

(ii) Synthesis of the iron-dextran complex

120 kg of the above-mentioned dextran in the form of an 18% solution was mixed with 300 kg of FeCk6H-O.

180 kg of Na2CO3 as a saturated aqueous solution were added to this mixture with stirring, and then the pH of the mixture was adjusted to 11.5 with 38 liters of concentrated aqueous NaOH solution (27% w / v).

The mixture thus obtained was heated above 100 ° C until a black or dark brown colloidal solution was obtained, which was filtered through a 0.45 µm filter and then cooled. After cooling, the solution was neutralized with 25 liters of concentrated hydrochloric acid to a pH of 5.60 and purified using membrane processes to bring the solution chloride content below 1.1% based on a 10% w / v solution. iron.

The hydroxy acid in the form of 6 kg of citric acid was then added, the pH of the mixture was adjusted to above 8.0 with NaOH and stabilized by increasing the temperature above 100 ° C for 60 minutes.

The pH was then adjusted to 5.6 with concentrated hydrochloric acid. If the chloride content of the solution is lower than desired, it is adjusted by adding NaCl.

The solution was filtered through a 0.45 µm (or 0.2 µm) membrane filter.

The solution was spray dried to give the iron-dextran complex as a powder.

This powder is suitable for the preparation of iron-dextran liquid formulations containing about 10% w / v. iron.

EXAMPLE 3 (i) Hydrolysis and hydrogenation of dextran

This synthesis step was performed as described above in Example 2.

(ii) Synthesis of iron-dextran complex kg of dextran obtained as described above in the form of a 10% solution was mixed with 400 kg of FeCk6H-O.

To this mixture was added 232 kg of Na2CO3 in the form of a saturated aqueous solution under stirring, and then the pH of this mixture was adjusted to 11.5 with 60 liters of concentrated aqueous NaOH solution (27% w / v).

The above-obtained mixture was heated at over 100 ° C until a black or dark brown colloidal solution was obtained, filtered through a 0.45 µm filter, and then cooled. After cooling, the solution was neutralized with 15 liters of concentrated hydrochloric acid to pH 5.60 and purified using membrane processes to bring the solution chloride content below 1.8%, based on a 20% w / v solution. iron.

PL 195 582 B1

The hydroxy acid in the form of 8 kg of citric acid was then added, the pH was adjusted to above 8.0 with NaOH, and the solution was stabilized by increasing the temperature above 100 ° C for 60 minutes.

The pH was then adjusted to 5.6 with concentrated hydrochloric acid. If the chloride content of the solution is lower than desired, it is adjusted by adding NaCl.

The solution was then filtered through a 0.45 µm (or 0.2 µm) membrane filter.

Finally, the solution was spray dried to give the iron-dextran complex as a powder. The powder is suitable for the preparation of iron-dextran liquid preparations containing 20% w / v iron.

In all three examples, the iron-dextran complex was obtained in powder form with a yield of greater than 95%, based on the iron used in the process.

Claims (12)

1. Iron (III) oxyhydroxide hydrogenated dextran association complex of 700-1400 daltons weight average molecular weight (Mw), preferably about 1000 daltons, number average molecular weight (Mn) 400-1400 daltons, with 90% by weight of dextran having the weight and the Mw of the 10 wt% dextran fraction with the highest molecular weight is less than 3,200 daltons, and this hydrogenated dextran has been purified using membrane processes at a cut-off of 340-800 daltons, for use as a therapeutic agent component for prophylaxis or treatment iron deficiency in animals or humans by parenteral administration. 2. The association complex according to claim 1 The process of claim 1, wherein it is the sole ingredient or one of the ingredients of the dry powder. 3. The association complex according to claim 1, The process of claim 2, wherein said powder has an iron content of 15-45% by weight. 4. The association complex according to claim 1, The process of claim 1, wherein it is dissolved or dispersed in an aqueous liquid. 5. The association complex according to claim 1 The process of claim 4, wherein it is dissolved or dispersed in the aqueous liquid in such an amount that the iron content of the resulting solution or dispersion is 5-20% w / v. 6. A method for producing an iron (III) oxyhydroxide hydrogenated dextran association complex according to claim 1. The process of claim 1, wherein the association complex is prepared by reducing the molecular weight by hydrolysis and converting the aldehyde end groups of the dextran to alcohol groups by hydrogenating the dextran; combining the hydrogenated dextran in the form of an aqueous solution with at least one water-soluble iron (III) salt; a base is added to the resulting solution to form iron (III) hydroxide and the resulting mixture is heated by converting iron (III) hydroxide to iron (III) oxyhydroxide in the form of an associative compound with dextran, characterized in that after hydrolysis but before combining with water-soluble iron (III) salt, the dextran is purified using one or more membrane processes with a cut-off suitable for retaining dextran with a molecular weight greater than 2700 daltons, optionally followed by further hydrolysis, followed by one or more membrane processes at cutoff 340-800dalton. 7. The method according to p. 6, characterized in that in the following stages: an aqueous solution is prepared containing the obtained hydrogenated dextran and at least one water-soluble iron (III) salt; the pH of this aqueous solution is adjusted to above 10 by addition of a base; this mixture is heated to above 100 ° C until a black or dark brown colloidal solution is obtained, filterable through a 0.45 µm filter; and purifying and stabilizing the solution by filtration, heating, and membrane processes, and adding one or more stabilizers, and optionally drying the solution to obtain the desired iron-dextran compound as a stable powder. 8. The method according to p. The process of claim 6, characterized in that the hydrogenation of the dextranes is carried out with sodium borohydride in an aqueous solution. PL 195 582 B1 9. The method according to p. The process of claim 7, characterized in that the solution is stabilized by adding at least one salt of an organic hydroxy acid, preferably selected from citrates. 10. Use of an association complex of iron (III) oxyhydroxide and hydrogenated dextran with a weight average molecular weight (Mw) of 700-1400 daltons, preferably about 1000 daltons, the number average molecular weight (Mn) of 400-1400 daltons, with 90% by weight of the dextran having a molecular weight of less than 2,700 daltons and the Mw of the 10 wt% dextran fraction with the highest molecular weight is less than 3,200 daltons, and this hydrogenated dextran has been purified using membrane processes at a cut-off of 340-800 daltons to produce a prophylactic parenteral medicament or the treatment of iron deficiency anemia in animals or humans. 11. A method of producing an injection fluid containing iron-dextran compound, characterized in that the associative complex according to claim 1, 1 as a dry powder is dissolved in an aqueous medium, if necessary the pH is adjusted, optionally a stabilizer is added and the liquid is sterilized by filtration before filling into ampoules or vials or by autoclaving after filling into ampoules or vials. 12. A method of producing an injection fluid containing iron-dextran compound, characterized in that the fluid obtained by the method of claim 1 6 is purified, the iron content and the pH value is adjusted, stabilized and sterilized by filtration before filling into ampoules or vials or by autoclaving after filling into ampoules or vials.